Showing papers in "Obstetrical & Gynecological Survey in 2004"
TL;DR: Mutations in GPR54, a G protein-coupled receptor gene, cause autosomal recessive idiopathic hypogonadotropic hypogOnadism in humans and mice, suggesting that this receptor is essential for normal gonadotropin-releasing hormone physiology and for puberty.
Abstract: The first known step in sexual maturation at puberty is the secretion of gonadotropin-releasing hormone (GnRH) by the hypothalamus. Pubertal changes also include accelerated linear growth and adrenal maturation. The authors used complementary genetic approaches in both humans and mice to study a gen
754 citations
TL;DR: As compared with placebo, letrozole therapy after the completion of standard tamoxifen treatment significantly improves disease-free survival.
Abstract: Tamoxifen, given for 5 years after surgery for hormone-dependent breast cancer, prolongs disease-free survival and overall survival. No added effect is noted with more than 5 years of treatment. This study, enrolling postmenopausal women who had been treated for early-stage breast cancer, was intended to show whether letrozole improves the outcome after tamoxifen therapy is withdrawn. Letrozole is an aromatase inhibitor that suppresses estrogen production. Using a randomized, double-blind design, 5187 women who had taken adjuvant tamoxifen therapy for 4.5 to 6 years were assigned to receive 2.5 mg letrozole or placebo orally each day for 5 years. All participants were age 50 and older when tamoxifen therapy began, and all had a tumor that was positive for estrogen receptors and/or progesterone receptors. After a median follow up of 2.4 years, there were 207 local or metastatic recurrences of breast cancer or new primary cancers in the other breast, 75 in the letrozole-treated group and 132 in placebo recipients. The estimated 4-year disease-free survival rates were 93% and 87%, respectively. The hazard ratio for cancer in the letrozole group was 0.57. Women with negative lymph nodes did at least as well as those with node-positive disease when given letrozole. Overall survival rates were 96% in the letrozole group and 94% in placebo patients, with a hazard ratio in the former group of 0.76. Hot flashes, arthritislarthralgia, and myalgia were more frequent in the letrozole group, but vaginal bleeding occurred more often in the placebo group. Comparable numbers of patients (4.5% and 3.6%, respectively) discontinued treatment because of toxic effects. A trend was noted toward more frequent newly diagnosed osteoporosis in patients given letrozole. The investigators concluded that letrozole should be considered for postmenopausal women with hormone receptor-positive breast cancer who have completed 5 years of tamoxifen therapy. The optimal duration of letrozole treatment remains to be determined.
745 citations
TL;DR: The therapeutic effects of alendronate were sustained, and the drug was well tolerated over a 10-year period, and safety data did not suggest that prolonged treatment resulted in any loss of benefit.
Abstract: This multinational randomized double-blind trial, the Alendronate Phase III Osteoporosis Treatment Study, examined the results of alendronate therapy in postmenopausal women with osteoporosis who now have been followed for 10 years. A total of 227 women completed all phases of the study. Those participating were assigned to receive 5 or 10 mg of alendronate orally or placebo each day. The primary end point was the change in bone mineral density (BMD) in the lumbar spine. BMD also was measured at the femoral neck, trochanter, total proximal femur, forearm region, and the total body. From 17% to 31% of women in the various treatment groups had preexisting vertebral fractures. BMD continued to increase in the later years of the study in women given 5 or 10 mg of alendronate daily. The mean cumulative increase after 10 years in women taking 10 mg daily was 13.7%. Markers of bone remodeling (urinary N-telopeptides of type I collagen, bone-specific alkaline phosphatase) decreased, and this effect continued through 10 years of treatment. These markers increased within a year after alendronate was discontinued, although mean levels remained below baseline. There were no significant group differences in new vertebral fractures. The 3 groups also had similar safety profiles in the last 3 years of the study. No deaths were ascribed to alendronate therapy. Alendronate therapy continued to be effective over 10 years in these postmenopausal women, as estimated by both BMD measurements and effects on bone remodeling. The antifracture effect of alendronate did not appear to decrease over time.
652 citations
TL;DR: Adjunctive RT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence, but should be limited to patients whose risk factors fit a high intermediate risk definition.
Abstract: Between June 1987 and July 1995, 448 women with endometrial cancer were enrolled in a prospective, randomized trial comparing the use of postoperative radiation versus no postoperative treatment. Participants had stage IB, IC, II, or IIB endometrial adenocarcinoma with an intermediate risk of recurrence (that is, tumor with any degree of myometrial invasion, adenocarcinoma of any grade, and no evidence of lymph node involvement). In addition, an analysis was performed of 2 subgroups. High-risk patients had all of these risk factors: moderate to poorly differentiated tumor, presence of lymphvascular invasion, and myometrial invasion to the outer third; they were 50 years of age or older with 2 of the 3 risk factors; or they were 70 years of age or older and had one additional risk factor. Women who did not qualify for the high-risk subgroup were considered in the low-risk subgroup. Three hundred ninety-two participants met all eligibility requirements for inclusion in the analysis. Two hundred two women were randomized to the whole pelvic radiation group, and 190 received no additional postoperative treatment. Otherwise, both groups had similar clinical and demographic characteristics. In the radiation therapy (RT) group, 13 patients refused postoperative treatment and 5 received less than the prescribed dose. In the no-treatment group, 2 patients received fall-dose postoperative RT. Twenty-four participants were lost to follow up within a median of 50 months. Overall median follow up was 68 months. Forty-four patients, 31 in the unirradiated group and 13 in the radiation group, developed disease recurrence. After a median follow up of 80 months, 15 of the women who recurred were alive with disease. In all, 66 women in the study died, 32 from disease or treatment-related causes. Women who received postoperative radiation therapy were less likely to have a recurrence of disease than those who had no additional treatment Among the 202 patients who had no postoperative treatment, 13 recurred in the vagina, 4 in the pelvis, 1 in the vagina and pelvis, and 13 had distant recurrences. In the RT group, 2 women, both of whom refused treatment with radiation, had a recurrence in the vagina. One other patient recurred in the vagina and pelvis, and 10 had distant recurrences. Patients who were treated with postoperative radiation therapy had a 58% lower risk of ever having a recurrence of disease than women who did not. The overall risk of recurrence in the first 24 months after treatment was 3% (90% confidence interval [CI], 0.02-0.06) for women who received RT and 12% (90% CI, 0.09-0.17) for women who had no additional treatment. The estimated cumulative risk of recurring in the vagina or pelvis within the first 24 months was 1.6% (90% CI, 0.6-3.9) for those in the RT group compared with 7.4% (90% CI, 4.9-11.0) for the no additional treatment group. In the 132 women who were in the high-risk subgroup, 28 (28 of 44; 64%) had a recurrence of disease and 22 died from disease (22 of 32; 67%). The estimated risk of recurrence for high-risk women was 0.46 (90% CI, 0.19-1.11) compared with 0.42 (90% CI, 0.21-0.83) for low-risk women. There were 2 deaths from intestinal injury associated with radiation treatrnent. Overall, there were 6 instances of bowel obstruction in the RT group and 1 in the no additional treatment group.
624 citations
TL;DR: A strategy to reduce overall fracture incidence will likely require lifestyle changes and a targeted effort to identify and develop treatment protocols for women with less severe low bone mass who are nonetheless at increased risk for future fractures.
Abstract: This study, based on data from the National Osteoporosis Risk Assessment, examined the effects of different treatment thresholds on fracture risk within a year after a measurement of bone mineral density (BMD). BMD is thesingle most important predictor of osteoporotic fractures in postmenopausal women having no previous fractures. The study population included 149,524 white postmenopausal women 50 to 104 years of age. At baseline, BMD was measured by peripheral bone densitometry at the heel, finger, or forearm. Fracture risk was followed over the next 12 months. A total of 2340 new osteoporotic fractures were reported by 2259 women. Hip fractures made up 17% of the total. As shown in Figure 1, lower baseline BMD values were associated with higher fracture rates (the number of women with fracture per 1000 person-years of follow up). Fracture rates were highest in women with the lowest T scores. More than 80% of women who reported having a fracture within 12 months had peripheral T scores higher than -2.5, and two thirds had T scores exceeding -2.0. Fracture rates were highest in these women but they occurred in only 18% of osteoporotic fractures and 26% of hip fractures. According to treatment guidelines formulated by the National Osteoporosis Foundation, 22.6% of women had T scores of 2.0 or less or -1.5 or less accompanied by 1 or more clinical risk factors. Fracture rates were lower in these women, but they constituted 45% of all osteoporotic fractures and 53% of hip fractures. It seems unlikely that a substantial reduction of osteoporotic fractures in postmenopausal women could be achieved solely by treating women with T scores of -2.5 or less. More attention must be given to women with moderate loss of bone mass who are nevertheless at increased risk of future fracture. The authors believe that nonpharmacologic measures such as weight-bearing exercise, strength training, and a healthy diet with adequate calcium should be tried as an initial measure.
492 citations
TL;DR: All obese women with PCOS should be screened for the presence of insulin resistance by looking for other stigmata of the insulin resistance syndrome such as hypertension, dyslipidemia, central obesity, and glucose intolerance.
Abstract: Approximately 50% to 70% of all women with polycystic ovary syndrome (PCOS) have some degree of insulin resistance, and this hormone insensitivity probably contributes to the hyperandrogenism that is responsible for the signs and symptoms of PCOS. Although uncertainty exists, early detection and tre
432 citations
TL;DR: For women aged 65 years or older, hormone therapy had an adverse effect on cognition, which was greater among women with lower cognitive function at initiation of treatment.
Abstract: Data from the Women’s Health Initiative Memory Study (WHIMS) were analyzed to determine whether conjugated equine estrogen (CEE) influences global cognitive function in women 65 to 79 years of age, and to compare its effects with those of CEE plus medroxyprogesterone acetate (MPA). Using a r
349 citations
TL;DR: The present report presents data from the Women’s Health Initiative Memory Study, which suggests an increased risk of dementia, but not mild cognitive impairment (MCI), in women given conjugated equine estrogens plus medroxyprogesterone acetate.
Abstract: Previous findings from the Women’s Health Initiative Memory Study (WHIMS) have suggested an increased risk of dementia, but not mild cognitive impairment (MCI), in women given conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA). The present report presents data from the
261 citations
TL;DR: Increased bone loss after menopause is associated with increased periosteal apposition, which partially preserves bone strength, and a strength index may be a helpful predictor of the risk of fracture.
Abstract: Although bone is lost after menopause, bone strength is also a function of structural attributes such as bone size. It is not clear whether periosteal apposition leads to increased bone size, or whether a strength index taking into account both bone density and bone size would predict the risk fracture better than estimates of bone density alone. In a prospective study, bone mass and the skeletal structure of the distal radius were examined by single-photon absorptiometry every other year in 108 women who were followed for a mean time of 15 years after menopause. Bone mineral density decreased progressively by a mean of 1.9% annually, and bone mineral content declined by 1.3% per year between menopause and age 67 years. Medullary diameter increased steadily by 1.1% per year and periosteal diameter by 0.7%. The cross-sectional moment of inertia increased 3.1% annually and the section modulus by 2.1%. The bone strength index, which incorporates bone mass and the structural appearance of bone, was estimated as the product of section modulus and bone mineral density. The index declined annually by 0.7% over the course of the study, but the change was not significant until 14 years after menopause. Expansion of the medullary diameter correlated with expanding periosteal diameter. Women in the highest quartile of medullary expansion experienced more loss of bone mineral density and had greater periosteal apposition than those in the lower quartile. Postmenopausal serum estradiol levels correlated with changes in periosteal diameter and bone mineral density. Finally, a 1 standard deviation decrease in the bone strength index at baseline was associated with a risk ratio of 3.8 for distal radial fracture. In addition to losing bone density after menopause; women undergo an increase in bone size resulting from periosteal apposition. The latter change helps preserve bone strength. The bone strength index calculated in this study could help to predict fracture risk during follow up.
249 citations
TL;DR: Primary elective cesarean performed on a patient’s request now comprises 4% to 18% of all cesarans and 14% to 22% of electivecesareans in reported series.
Abstract: Primary elective cesarean performed on a patient’s request now comprises 4% to 18% of all cesareans and 14% to 22% of elective cesareans in reported series. Patients most commonly choose cesarean because of tocophobia, or fear of childbirth. Almost two thirds of obstetricians surveyed are willing to
230 citations
TL;DR: Paroxetine CR is a well-tolerated alternative to hormone replacement therapy and other measures for treating hot flashes in menopausal women, although the optimal dose and the durability of responses remain to be determined.
Abstract: Hot flashes are the most common complaint of women entering menopause, and they can continue for as long as 15 years. Hormone replacement with estradiol or progestational agents has been standard treatment, but might not be suitable for some women such as those with a history or increased risk of breast cancer. Recent studies suggest that antidepressant drugs that inhibit serotonin reuptake such as venlafaxine and fluoxetine could significantly counter vasomotor symptoms accompanying menopause. This randomized, double-blind, placebo-controlled study enrolled 165 menopausal women aged 18 and over at 17 diverse sites in the United States. All had been experiencing 2 to 3 hot flashes each day, and they had not used hormone replacement therapy for at least 6 weeks. Women with signs of active cancer or who were receiving chemotherapy or radiotherapy were excluded. Participants were randomized to receive 12.5 or 25 mg daily of paroxetine CR (controlled release) or a placebo for 6 weeks. The 3 groups were clinically comparable. The women kept a daily diary of symptoms and completed a symptom-assessment questionnaire after 1, 3, and 6 weeks. Similar and significant reductions in daily hot flashes were observed in both groups of actively treated women (Fig. 1). After 6 weeks, the lower and higher doses of paroxetine reduced hot flash scores by 62% and 65%, respectively, compared with a drop of 38% in the placebo group. The differences persisted after adjusting for age, history of breast cancer, past psychiatric disorder, and use of antiestrogens. Improvement was evident within 1 week of starting treatment and persisted to the end of the study. (Fig. 2). The chance of a response was more than 2.5 times greater for women taking the higher dose of paroxetine than for placebo recipients. Responses were independent of significant changes in mood or anxiety level. Adverse effects occurred in 58% of women given paroxetine CR and in 54% of placebo patients. The most common such events associated with paroxetine CR were headache, nausea, and insomnia. A majority of side effects were mild or moderate. Paroxetine CR is a well-tolerated alternative to hormone replacement therapy and other measures for treating hot flashes in menopausal women, although the optimal dose and the durability of responses remain to be determined.
TL;DR: Surgical correction of the cardiac lesion prior to pregnancy was associated with better pregnancy outcome and patients inNYHA class I/II had a better maternal and fetal outcome than those in NYHA class III/IV.
Abstract: Although maternal mortality has declined steadily over the past 2 decades, the proportion of heart disease among all causes of mortality has remained unchanged. Reported rates of heart disease in pregnancy range from 0.9%to 3.7%. The authors retrospectively studied 207 pregnancies encountered in the years 1994 to 2000 at a tertiary care center. These women had cardiac disease and delivered at or after 28 weeks gestation. Those whose cardiac status was becoming worse or who were already in New York Heart Association (NYHA) class III/IV were hospitalized. Heparin treatment was stopped when labor began. Labor was induced only for obstetric reasons, using oxytocin cautiously. All women were kept propped up and given oxygen intermittently, and the second stage of labor was shortened if indicated by using outlet forceps or vacuum extraction. A majority of these women were multigravidas and ranged in age from 18 to 35 years. Rheumatic heart disease was present in 88% of pregnancies, most often in the form of isolated mitral stenosis. Another 24 women had congenital heart disease. Pregnancies occurred an average of 6.6 years after the diagnosis of heart disease, but in 13% of cases, it was diagnosed during the index pregnancy. One in 5 women were in NYHA class III/IV at the first antenatal visit. New-onset cardiac complications occurred in 30% of pregnancies. Women in NYHA classes I/II had fewer complications, and their infants were heavier at birth than those in the class III/IV group. The hospitalization rate before 37 weeks gestation was 55%, and the mean hospital stay was 2 weeks. All but 20% of women delivered vaginally. The cesarean section rate was 46% in women with the most advanced cardiac disease. Fetal complications occurred in 20% of pregnancies but there were no infant deaths. Cardiac interventions were necessary before pregnancy in 61% of women with rheumatic heart disease. Both maternal and fetal outcomes were better in women with prosthetic valves, a large majority of whom remained in NYHA class I/II. Ten women had interventions while pregnant; one of them developed congestive heart failure during labor. None of 41 newborn infants whose mothers had received anticoagulants had congenital malformations. These results emphasize the need for prepregnancy counseling of women with heart disease to ensure close surveillance during pregnancy. Early diagnosis is important, as is the surgical correction of cardiac lesions when indicated.
TL;DR: The authors recommend that sedentary adults who are overweight begin by exercising at moderate intensity for at least 150 minutes per week, when appropriate, higher exercise levels should be adopted, aiming at an hour a day as advised by the Institute of Medicine.
Abstract: To test the hypothesis that longer and more intense exercise will enhance long-term weight loss, 201 sedentary women 27 to 40 years of age were enrolled in a randomized trial. The participants, whose baseline body mass index ranged from 27 to 40 kg/m 2 , were in a university-based weight control program. They were assigned to 1 of 4 groups that exercised at moderate or vigorous intensity for a moderate to long duration. Estimated energy expenditure was 1000 or 2000 kcal per week. All women were asked to reduce their energy intake to 1200 to 1500 kcal per day and their dietary fat intake to 20% to 30% of total energy intake. Nearly 95% of participants completed 12 months in the study. All participants were sedentary at the outset, exercising less than 3 days per week for less than 20 minutes. They were instructed to exercise, unsupervised, for 5 days a week, primarily by walking; motorized treadmills were provided. Bouts of exercise lasting at least 10 minutes were prescribed in terms of both percentage of age-predicted maximal heart rate and perceived exertion using the Borg scale. The women attended an average of 79% of group sessions in the first 6 months and 71% over the entire 12-month study period. Mean weight loss was significant in all groups, ranging from 8.9 kg with long-lasting vigorous exercise to 6.3 kg with moderate exercise of moderate duration. There were no significant between-group differences. Mean cardiorespiratory fitness also increased significantly in all groups, most markedly (22%) with vigorous, high-duration exercise. The least improvement, an increase of 13.5%, was in the group exercising at moderate intensity for a moderate time. Again, there were no differences between groups. Weight loss at 12 months correlated with the level of physical activity at both 6 and 12 months. Women exercising less than 150 minutes per week lost a mean of 4.7% body weight, contrasting with 13.6% for those exercising at least 200 minutes per week. There were no significant group differences in energy intake. The authors recommend that sedentary adults who are overweight begin by exercising at moderate intensity for at least 150 minutes per week. When appropriate, higher exercise levels should be adopted, aiming at an hour a day as advised by the Institute of Medicine.
TL;DR: Among patients who have recently had an acute coronary syndrome, an intensive lipidlowering statin regimen provides greater protection against death or major cardiovascular events than does a standard regimen.
Abstract: background Lipid-lowering therapy with statins reduces the risk of cardiovascular events, but the optimal level of low-density lipoprotein (LDL) cholesterol is unclear. methods We enrolled 4162 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and compared 40 mg of pravastatin daily (standard therapy) with 80 mg of atorvastatin daily (intensive therapy). The primary end point was a composite of death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization (performed at least 30 days after randomization), and stroke. The study was designed to establish the noninferiority of pravastatin as compared with atorvastatin with respect to the time to an end-point event. Follow-up lasted 18 to 36 months (mean, 24). results The median LDL cholesterol level achieved during treatment was 95 mg per deciliter (2.46 mmol per liter) in the standard-dose pravastatin group and 62 mg per deciliter (1.60 mmol per liter) in the high-dose atorvastatin group (P<0.001). Kaplan–Meier estimates of the rates of the primary end point at two years were 26.3 percent in the pravastatin group and 22.4 percent in the atorvastatin group, reflecting a 16 percent reduction in the hazard ratio in favor of atorvastatin (P=0.005; 95 percent confidence interval, 5 to 26 percent). The study did not meet the prespecified criterion for equivalence but did identify the superiority of the more intensive regimen. conclusions Among patients who have recently had an acute coronary syndrome, an intensive lipidlowering statin regimen provides greater protection against death or major cardiovascular events than does a standard regimen. These findings indicate that such patients benefit from early and continued lowering of LDL cholesterol to levels substantially below current target levels.
TL;DR: The choice of treatment for endometrial hyperplasia is dependent on patient age, the presence of cytologic atypia, the desire for future childbearing, and surgical risk; however, women with atypicalhyperplasia should be treated with hysterectomy unless other factors preclude surgery.
Abstract: Endometrial hyperplasia is a precursor to the most common gynecologic cancer diagnosed in women: endometrial cancer of endometrioid histology. It is most often diagnosed in postmenopausal women, but women at any age with unopposed estrogen from any source are at an increased risk for developing endometrial hyperplasia. Hyperplasia with cytologic atypia represents the greatest risk for progression to endometrial carcinoma and the presence of concomitant carcinoma in women with endometrial hyperplasia. Abnormal uterine bleeding is the most common presenting symptom of endometrial hyperplasia. Specific Pap smear findings and endometrial thickness per ultrasound could also suggest the diagnosis. Unopposed estrogen in women taking hormone replacement therapy increases the risk of endometrial hyperplasia. Tamoxifen has demonstrated its efficacy in treating women at risk for breast cancer, but it increases the risk of endometrial hyperplasia. The choice of treatment for endometrial hyperplasia is dependent on patient age, the presence of cytologic atypia, the desire for future childbearing, and surgical risk. Endometrial hyperplasia without atypia responds well to progestins. However, women with atypical hyperplasia should be treated with hysterectomy unless other factors preclude surgery. Target audience Obstetricians & Gynecologists, Family Physicians. Learning objectives After completion of this article, the reader should be able to describe the definition and classification of endometrial hyperplasia, to outline the clinical features of a patient with endometrial hyperplasia, to point out the natural history of endometrial hyperplasia, and to summarize the diagnostic options for patients with endometrial hyperplasia.
TL;DR: In survivors with spontaneous menstrual cycles, the results indicate a diminished ovarian reserve and cessation of fertility may occur much earlier than anticipated, and adult survivors with spontaneously cycles should be informed hereof to plan childbearing.
Abstract: Seventy percent of children with cancer survive. Radiation and chemotherapy may, however, impair ovarian function. The aim of this population-based study was to achieve a comprehensive knowledge of the degree of ovarian damage. Ovarian function was evaluated in 100 childhood cancer survivors and 21 controls of similar age. Menstrual cycle pattern was recorded, and strictly timed ovarian sonography and hormonal assessment were performed. The median age of the survivors was 5.4 yr (range, 0.1–15.3) at the time of diagnosis and 25.7 yr (18.5–44.4) at study entry. Seventeen survivors with premature ovarian failure had follicle-depleted or nondetectable ovaries, elevated FSH and LH, and immeasurable inhibin B. Thirteen survivors used oral contraception. Survivors with spontaneous menstrual cycles (n = 70) had smaller ovarian volume per ovary than controls (median, 4.8 vs. 6.8 cm3; P < 0.001) and a lower number of antral follicles per ovary (median, 7.5 vs. 11; P < 0.001). Further, they had lower inhibin B leve...
TL;DR: First-trimester screening for trisomies 21 and 18 on the basis of maternal age, maternal levels of free beta human chorionic gonadotropin and pregnancy-associated plasma protein A, and measurement of fetal nuchal translucency has good sensitivity at an acceptable false positive rate.
Abstract: Screening for aneuploid pregnancies is routinely carried out after 15 weeks gestation. It is approximately 65% sensitive and has a false-positive rate of 5%. In this multicenter study, a number of markers of aneuploidy were used to screen pregnancies at 74 to 97 days gestation for trisomies 21 and 18. Screening incorporated maternal age, levels of pregnancy-associated plasma protein A and free β-human chorionic gonadotropin, and 3 ultrasound measurements of nuchal translucency. These measurements were monitored for quality by comparing values with norms of the Fetal Medicine Foundation. The study population of 8514 women with singleton pregnancies excluded those with recent vaginal bleeding, pregestational diabetes, or pregnancy resulting from donor oocytes. Screening identified 85.2% of 61 cases of Down syndrome (trisomy 21) with a false-positive rate of 9.4%. Adjusting the cutoff value to correlate with a false-positive rate of 5%, sensitivity decreased to 78.7%. A false-positive rate of 1% would result in detecting 63.9% of cases. The combined approach detected 89.8% of fetuses with trisomy 21 in women aged 35 and older, with a false-positive rate of 15.2%. Combined screening identified 90.9% of 11 cases of trisomy 18 with a 2% false-positive rate. Among older women, all fetuses with trisomy 18 were identified. In addition, screening identified 4 of 5 cases of trisomy 13. The use of combined screening measures in the first trimester detects trisomies 18 and 21 as well as second-trimester screening, even after controlling for potentially nonviable pregnancies. Sensitivity is good and the rate of false-positive results is acceptable. Screening early in pregnancy offers patients more privacy, earlier results, and safer reproductive alternatives.
TL;DR: This prospective community-based study was an attempt to identify risk factors other than sociocultural barriers that arerelated to poor lactation outcomes for suboptimal infant breastfeeding behavior (SIBB), delayed lactation, and excessive neonatal weight loss.
Abstract: Even mothers who strongly want to breast feed their infants could have difficulty getting started. This prospective community-based study was an attempt to identify risk factors other than sociocultural barriers that arerelated to poor lactation outcomes. Risk factors were sought for suboptimal infant breastfeeding behavior (SIBB), delayed lactation, and excessive neonatal weight loss. Participants gave birth to a healthy single infant at term and were willing to try breast feeding exclusively for at least 30 days. Trained lactation consultants provided guidance in such areas as correct positioning, demand feeding, and avoidance of supplements, and also evaluated infant breastfeeding behavior using the Infant Breast-feeding Assessment Tool. Weight loss exceeding 10% of birth weight on day 3 was considered excessive. The mean maternal age was 30.6 years and 56% of mothers were primiparous. Nearly 80% of subjects were non-Hispanic whites. The average educational level was high. These mothers expressed strongly positive attitudes toward breast feeding. SIBB was found in 49% of infants at baseline, 22% on day 3 and 14% on day 7. It correlated significantly with primiparity on days 0 and 3, with cesarean section (day 0 in multiparas), and with flat or inverted nipples. Other significant correlates of SIBB included using nonbreast milk fluids in the first 2 days of life, use of a pacifier, stage II labor lasting longer than 1 hour, and a maternal body mass index (BMI) greater than 27 kg/m 2 . Lactation was delayed in 22% of women, more frequently in primiparas, after cesarean section, and women having a prolonged second stage of labor, a high material BMI, flat or inverted nipples, or (in primiparas) a birth weight greater than 3600 g. Excessive weight loss was observed in 12% of neonates. It correlated with primiparity, a long labor, the use of labor medication (by multiparas), and infant status at birth. Excessive weight loss was 7.1-fold more likely if lactation was delayed and 2.6-fold more likely if SIBB was present on the first day of life.
TL;DR: LEEP and laser cone treatments were associated with significantly increased risk of pPROM, and care should be given to treatment of CIN in women of reproductive age, especially when treatment might reasonably be delayed or targeted to high-risk cases.
Abstract: Effective treatment of cervical intraepithelial neoplasia (CIN) can prevent invasive cervical cancer. The trend away from cold-knife conization toward more conservative procedures continues, but it is possible that excisional or ablative treatments might increase the risk of preterm delivery by lessening the mechanical support lent by a shortened cervix. These procedures also could impair local immunity by destroying glandular epithelium, and they might alter the bacterial flora in the cervicovaginal region. This retrospective cohort study, carried out at a colposcopy clinic in Auckland, New Zealand in the years 1988-2000, compared delivery outcomes in 652 women treated for CIN by laser conization, laser ablation, or a loop electrosurgical excision procedure (LEEP) and 426 untreated women. All participants carried a singleton pregnancy to at least 20 completed weeks of gestation. The overall rate of preterm delivery (before 37 weeks gestation) was 13.8%. The most common cause, identified in 45% of cases, was premature rupture of membranes (pPROM). Rates of total pretrerm deliveries, pPROM, and spontaneous preterm labor were higher in treated than in untreated women. Preterm delivery was iatrogenic in 2.9% of the treated group and 5.2% of the untreated group. Adjusted relative risk (aRR) figures showed that treating CIN was not associated with an increased risk of total or spontaneous preterm deliveries, but a single laser conization treatment or LEEP was associated with an increased risk of pPROM leading to preterm delivery. The risk of pPROM increased with an increasing height of excised cervical tissue. Women with a vertical cone height of at least 1.7 cm of tissue removed had a greater than 3-fold increase in risk of preterm delivery compared with untreated women (aRR, 3.6). The risk of pPROM increased linearly with increasing cone height; no threshold value was identified. The risk of all preterm deliveries increased significantly with increasing cone height. Treatment variables did not interact significantly with age, parity, or smoking during pregnancy, Mode of treatment did not relate to cone height. Women who are aware of the risk of preterm delivery associated with treating CIN will be likelier to present at an early stage for antibiotic and steroid treatment. Cervical cerclage might have a role in managing women whose ultrasound studies show progressive cervical shortening during pregnancy.
TL;DR: The bulk of significant medical literature over the last century is summarized to provide an accurate statement about what the authors know and what they do not know about neonatal circumcision, including its history, epidemiology, medical benefits, complications, contraindications, techniques, management for pain, and current controversies.
Abstract: Untimely old, circumcision has elicited more controversy and war of words than any surgical procedure in history. Although previous claims of benefits like curing masturbation, gout, epilepsy, and even insanity were no doubt absurd, important research has shed light on real medical benefits of circu
TL;DR: A high incidence of cerebral white matter abnormality at term in an unselected population of premature infants is confirmed, which is predominantly a result of noncystic injury in the extremely immature infant.
Abstract: More very-low-birth-weight (VLBW) infants are surviving today, but they could be challenged neurodevelopmentally by cerebral palsy, poor school performance, or behavioral disorder. This longitudinal population-based study used magnetic resonance imaging to determine the nature and extent of abnormalities in white and gray matter of the brain in 100 consecutive premature infants admitted to neonatal intensive care. They made up 98% of all VLBW infants admitted in a 26-month period in 1998 to 2000. Ten healthy term infants were scanned in the week of their due date. Images were graded for white matter (WM) abnormality in a blinded manner by a neuroradiologist experienced in pediatric magnetic resonance imaging, and gray matter abnormality and development were scored independently. Criteria for evaluating WM included cysts, signal abnormality, volume loss, ventriculomegaly, carpus callosal thinning, and myelination. For assessing gray matter, the criteria were signal abnormality, gyration, and the subarachnoid space. The study infants had a mean gestational age of 27.9 weeks and a mean birth weight of 1063 g. Approximately one third of them remained oxygen-dependent at 36 weeks-corrected gestational age. Twenty of the 100 infants had moderate to severe WM injury. On univariate analysis, predictors for moderately severe WM abnormality included lower gestational age, maternal fever, proved infant sepsis at the time of delivery, the need for inotropic support, patent ductus arteriosus, grade III/IV intraventricular hemorrhage, and pneumothorax. Restricted intrauterine growth appeared to have a protective effect. Gray matter abnormality, identified in 27 infants, was closely related to the presence and severity of WM changes. Ten of 11 infants born before 26 weeks gestation exhibited a pattern of significant diffuse WM atrophy, ventriculomegaly, immature gyral development, and an enlarged subarachnoid space. These infants are at the highest risk for subsequent global motor and cognitive impairment. Altered WM structure and closely related abnormalities of gyral development are common findings in VLBW infants. Magnetic resonance imaging at term will likely prove to be a good way of predicting future neurodevelopmental problems and of selecting affected children for early intervention programs.
TL;DR: In this article, the authors used a slow freezing technique and dimethylsulfoxide as a cryoprotectant to extract 15 ovarian cortical pieces from a woman with breast cancer and transplant them in the lower abdominal wall.
Abstract: Patients with cancer might want to avoid infertility and premature menopause as sequelae of chemotherapy and other treatments. Most patients with cancer do not have time for ovarian stimulation as a prelude to in vitro fertilization (IVF). An alternative approach, which could also be useful for single women who do not want to use donor sperm and for children, is to cryopreserve oocytes, but this also requires several weeks of ovarian stimulation. Ovarian function has been preserved experimentally after orthotopic transplantation of frozen-thawed ovarian tissue and heterotopic grafting of fresh human ovarian cortical pieces. This study intended to restore fertility by subcutaneously transplanting frozen, banked ovarian tissue. One ovary was removed from a woman aged 30 years with breast cancer before starting gonadotoxic chemotherapy. Cortical pieces were cryopreserved using a slow freezing technique and dimethylsulfoxide as a cryoprotectant. The tissue was transplanted beneath the abdominal skin 6 years later, after the patient had entered menopause. There were an estimated 11,000 follicles that could potentially last for 12 months. All 15 ovarian cortical pieces were transplanted in the lower abdominal wall. Tissue was suppressed with a combination of follicle-stimulating hormone and human menopausal gonadotropin before every cycle of ovarian stimulation. Oocyte maturity was induced by recombinant human chorionic gonadotropin. Oocytes were retrieved 36 to 40 hours later and intracytoplasmic sperm injection was carried out. A lump was felt at the transplant site 85 days after transplantation, and ovarian endocrine function resumed (Fig. 1). Eight percutaneous oocyte retrievals were carried out over 8 months, 6 of them after ovarian stimulation. Eight of 20 oocytes taken from transplanted tissue were suitable for IVF. One of them fertilized normally and developed into a high-grade 4-cell-stage embryo 24 hours later that was transferred to the patient's uterus. This experience indicates that endocrine function and fertility could be restored by long-term cryopreservation of ovarian tissue.
TL;DR: Laroscopic excision of endometriosis significantly reduces pain and improves quality of life for up to 5 years and return of pain following laparoscopicexcision is not always associated with clinical evidence of recurrence.
Abstract: Encouraging short-term results were previously found in women having laparoscopic excision of endometriosis, with less pain and an improved quality of life. The present prospective observational cohort study enrolled 176women with histologically confirmed endometriosis after laparoscopic excision. Of these women, 135 were followed for up to 5 years and for an average period of 3.2 years. The women were 31 years of age on average at the time of surgery. More than two thirds had taken analgesia for pain, and most had received some form of hormonal treatment. The most common presenting features were nonmenstrual pelvic pain and dysmenorrhea. More than half of the women had stage III or IV endometriosis at the time of surgery. Operative complications included one case of inadvertent opening of the rectum. Two thirds of women reported being improved after surgery, whereas one fourth claimed to be worse. Approximately one third received analgesics during follow up, and approximately one fourth received hormonal treatment. More than 40% of patients requiring these treatments had further surgery. Nearly 60% of 54 women who attempted to conceive a child during follow up were successful, and 44% delivered a live infant. Pain scores were very significantly reduced at follow up. Estimated times to reoperation, projected to 5 years, are shown in Figure 1. Quality-of-life instruments indicated marked impairment at baseline but significant improvement after excision of endometriosis. Sexual activity also improved significantly. Laparoscopic excision has proved to be an effective approach to women with all stages of endometriosis who were followed for up to 5 years. Their quality of life improves appreciably, although it might not return to levels seen in women without the disease.
TL;DR: The reader should be able to describe the various types of HPV detection systems, to compare the various HPV detection methods against the currently available methods of monitoring, and to outline a potential post-treatment management plan for patients treated for HPV-associated cervical neoplasia.
Abstract: According to the current guidelines in most western countries, women treated for cervical intraepithelial neoplasia grade 3 (CIN 3) are followed for at least 2 years after treatment by cytology.High-risk human papillomavirus (hrHPV) infections are necessary for the development and maintenance of CIN 3. HrHPV testing could be used to improve monitoring of women treated for CIN 3. This has prompted numerous studies for the implementation of hrHPV testing in monitoring of women treated for CIN 3. Included in this review are 20 studies, published between 1996 and 2003, comparing hrHPV testing with either resection margins or cervical cytology to predict recurrent/residual disease, and 11 of them could be used in a meta-analysis. In the meta-analysis of the 11 studies, the negative predictive value (NPV) for recurrent/residual disease of hrHPV testing was 98% (95% CI 97-99%), that of resection margins 91% (95% CI 87-94%), and that of cervical cytology 93% (95% CI 90-95%). When hrHPV testing was performed in conjunction with cytology, the sensitivity was 96% (95% CI 89-99%), specificity was 81% (95% CI 77-84%), the associated positive predictive value (PPV) was 46% (95% CI 38-54%), and the NPV was 99% (95% CI 98-100%). Combined hrHPV and cytology testing yielded the best test characteristics. We propose to include hrHPV testing in conjunction with cytology for monitoring women treated for CIN 3. Some follow-up visits for women testing negative for both hrHPV and cytology can be skipped. In western countries, this could mean that for women double negative at 6 months, retesting at 12 months should be skipped while keeping the 24-month follow-up visit.
TL;DR: The reader should be able to outline the history of HELLP syndrome and describe the pathophysiology of HELLp syndrome, to summarize the clinical presentation and differential diagnosis of HellP syndrome, and to list the various management options.
Abstract: Preeclampsia/eclampsia has been recognized for centuries and continues to plague both the patient and the obstetrician. A severe variant, the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP), has been recognized for 50 years. Although much new data has been elucidated about t
TL;DR: Intrapartum/neonatal nevirapine appears to be a simple, inexpensive, and well-tolerated regimen for significantly reducing perinatal transmission of HIV-1 in less developed countries.
Abstract: Providing antiretroviral therapy to human immunodeficiency virus type 1 (HIV-1)-infected women at the onset of labor could offer a relatively simple and affordable means of preventing vertical transmission. The HIVNET 012 study team reported, in 1999, that a single-dose intrapartum/neonatal regimen of nevirapine significantly lowered the risk of mother-child transmission by 47% compared with a brief regimen of zidovudine. The 496 infants had been followed up for 14 to 16 weeks. Data now are available for these infants up to age 18 months. Participating mothers had been assigned to receive either 200 mg nevirapine at the onset of labor, with 2 mg/kg for the infant within 72 hours after birth (regimen A), or 600 mg zidovudine at the onset of labor, followed by 300 mg every 3 hours until delivery and then 4 mg/kg orally twice a day for 7 days for the infant (regimen B). Testing for HIV-1 estimated HIV-1 RNA up to age 1 year and HIV-1 antibody at age 18 months. The estimated risk of HIV-1 transmission was 10.3% with zidovudine and 8.1% in the nevirapine group at birth; 20% and 11.8%, respectively, by age 6 to 8 weeks; 22.1% and 13.5% by age 14 to 16 weeks; and 25.8% and 15.7% by age 18 months. In all, nevirapine was associated with a 41% reduction in the relative risk of HIV-1 transmission at last follow up (95% confidence interval, 16-59%). Multivariate analysis showed that highly significant factors, besides the treatment effect, included the baseline maternal viral load and CD4 cell count. Adjusting for breastfeeding status did not alter the treatment effect. Serious adverse infant events in the first 2 months after birth occurred in approximately 10% of both treatment groups, and events also were comparably frequent at age 18 months. Intrapartum/neonatal nevirapine appears to be a simple, inexpensive, and well-tolerated regimen for significantly reducing perinatal transmission of HIV-1 in less developed countries.
TL;DR: Elevated plasma myeloperoxidase concentration appears to be a marker of vulnerable coronary artery plaque, and it helps to identify patients at risk for major adverse cardiac events independently of evidence that myocardial necrosis is present.
Abstract: The entire process of arterial plaque formation has been linked with inflammation, and extensive infiltration of neutrophils and monocytes is observed in thrombosed plaque in patients with acute coronary disease. One possible means by which leukocytes could influence the stability of plaque is myeloperoxidase, a leukocyte enzyme that is present in elevated amounts in patients with cardiovascular disease. This study examined the possibility that plasma levels of myeloperoxidase might serve as a marker of plaque vulnerability in patients seen in the emergency department with chest pain. The study group included 604 such patients, seen sequentially, whose most frequent final diagnoses were suspected coronary syndrome and myocardial infarction (MI). Control subjects were healthy and had no historic or clinical evidence of coronary artery disease. Enzyme levels were estimated by an enzyme-linked immunosorbent assay. Patients were seen an average of 4 hours after the onset of chest pain. Plasma myeloperoxidase levels were significantly higher in the study group than in control subjects. They correlated weakly with peak levels of troponin T, C-reactive protein, and age, but not with white cell count. Patients having MI within 16 hours before presentation had especially high myeloperoxidase levels, and the incidence of MI increased with increasing quartiles of myeloperoxidase. Baseline levels were higher in patients who later required revascularization or had a major adverse cardiac event in the next 30 days or 6 months. Multivariate logistic regression analyses confirmed that elevated plasma myeloperoxidase independently predicted an increased risk of MI, the need for revascularization, and major coronary events. Baseline levels helped to identify patients at risk even if troponin T was absent. Plasma myeloperoxidase concentration appears to be a marker of vulnerable coronary artery plaque. It helps to identify patients at risk for major adverse cardiac events independently of evidence that myocardial necrosis is present.
TL;DR: It is well known that preterm birth increases the risk of cerebral palsy (CP), but more than half of affected children are born at term and the prevalence of CP in term infants has not declined in recent years.
Abstract: It is well known that preterm birth increases the risk of cerebral palsy (CP), but more than half of affected children are born at term and the prevalence of CP in term infants has not declined in recent years. Because there is evidence that chorioamnionitis could substantially raise the risk of CP
TL;DR: A diagnostic approach that aims to separate IUGR resulting from placental disease from constitutionally small fetuses and those with other underlying etiologies needs to integrate multiple imaging modalities.
Abstract: UNLABELLED Normal fetal growth depends on the genetically predetermined growth potential and is modulated by fetal, placental, maternal, and external factors Fetuses with intrauterine growth restriction (IUGR) are at high risk for poor short- and long-term outcome Although there are many underlying etiologies, IUGR resulting from placental insufficiency is most relevant clinically because outcome could be altered by appropriate diagnosis and timely delivery A diagnostic approach that aims to separate IUGR resulting from placental disease from constitutionally small fetuses and those with other underlying etiologies (eg, aneuploidy, viral infection, nonaneuploid syndromes) needs to integrate multiple imaging modalities In placental-based IUGR, cardiovascular and behavioral responses are interrelated with the disease severity Ultrasound assessment of fetal anatomy, amniotic fluid volume, and growth is complementary to the Doppler investigation of fetoplacental blood flow dynamics A diagnostic approach to IUGR combining these modalities is presented in this review TARGET AUDIENCE Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES After completion of this article, the reader should be able to describe the development of the placental interface, to outline the mechanisms of placental insufficiency, and to list the manifestations of placental insufficiency and the tests that can be used to diagnose fetal growth restriction
TL;DR: The reader should be able to list the mechanisms of teratogenicity, to describe the intraoperative monitoring of a pregnant patient undergoing surgery, and to outline the particular issues associated with providing anesthesia to a pregnant patients undergoing cardiac and neurosurgical procedures.
Abstract: The need for anesthesia and surgery during pregnancy occurs in 1.5% to 2.0% of all pregnancies. Each year, over 75,000 pregnant women in the United States undergo nonobstetric surgery. The operations include those directly related to pregnancy (e.g., cerclage), those indirectly related to pregnancy (e.g., ovarian cystectomy), and those unrelated to gestation (e.g., appendectomy, cholecystectomy). The diagnosis of any medical condition requiring surgical intervention in pregnancy often raises questions about the safety of both surgery and anesthesia in these patients. This controversy was primarily attributed to the lay press speculations that surgery and anesthesia in pregnancy could pose hazards to the mother and fetus. Despite these concerns, the safety of nonobstetric surgery and anesthesia in pregnancy has been well established, and many pregnant women are safely anesthetized everyday without ill effects for the mother or fetus.